Kinase inhibitors

1. A compound of the general formula:

or pharmaceutically acceptable salts, hydrates, solvates, crystal forms or diastereomers thereof, wherein:

D is

where X 1 , X 2 , X 3 , X 4 are optionally substituted carbon, or one of X 1 , X 2 , X 3 , X 4 is N; R2 is 0–4 substituents independently chosen from H, halogen, C 1-4 alkyl, CH 2 F, CHF 2 , CF 3 , OCF 3 , aryl, hetaryl, C 1-4 alkylOC 1-4 alkyl, C 1-4 alkylOaryl, C 1-4 alkylNR3R4, CO 2 R3, CONR3R4, CONR3SO 2 R4, NR3R4, C 1-4 alkylNR3R4, nitro, NR3COR4, NR5CONR3R4, NR3SO 2 R4, C 1-4 alkylNR3COR4, C 1-4 alkylNR5CONR3R4, C 1-4 alkylNR3SO2R4; and R3, R4 are each independently H, halogen, CH 2 F, CHF 2 , CF 3 , C 1-4 alkyl, C 1-4 alkyl cycloalkyl, C 1-4 cyclohetalkyl, aryl, C 1-4 alkyl aryl, hetaryl, C 1-4 alkyl hetaryl, or may be joined to form an optionally substituted 3–8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; and R5 is selected from H, C 1-4 alkyl, halogen, CH 2 F, CHF 2 , CF 3 , aryl or hetaryl; and R6 is selected from H, C 1-4 alkyl, aryl, hetaryl, C 1-4 alkyl aryl, C 1-4 alkyl hetaryl;

R1 is H, C 1-4 alkyl, C 1-6 cycloalkyl;

Q is a bond, CH 2 , C 1-4 alkyl;

A is aryl, hetaryl optionally substituted with 0–3 substituents independently chosen from halogen, C 1-4 alkyl, CH 2 F, CHF 2 , CF 3 , OCF 3 , CN, NR8R9, aryl, hetaryl, C 1-4 aryl, C 1-4 hetaryl, C 1-4 alkylNR8R9, OC 1-4 alkylNR8R9, nitro, NR10C 1-4 NR8R9, NR8COR9, NR10CONR8R9, NR8SO 2 R9, CONR8R9, CO 2 R8 where R8 and R9 are each independently H, C 1-4 alkyl, aryl or which together form an optionally substituted 4–8 membered ring which may contain a heteroatom selected from O, S, NR11, where R11 is C 1-4 alkyl, and R10 is selected from H, C 1-4 alkyl; and

W is selected from H, C 1-4 alkyl, C 2-6 alkenyl; where C 1-4 alkyl or C 2-6 alkenyl may be optionally substituted with C 1-4 alkyl, OH, OC 1-4 alkyl, NR12R13; and R12, and R13 are each independently H, C 1-4 alkyl, or may be joined to form an optionally substituted 3–8 membered ring optionally containing an atom selected from O, S, NR14 and R14 is selected from H, C 1-4 alkyl.

2. A compound according to claim 1 of the general formula II

or pharmaceutically acceptable salts, hydrates, solvates, crystal forms or diastereomers thereof, wherein:

D is

where X 1 , X 2 , X 3 , X 4 are optionally substituted carbon, or one of X 1 , X 2 , X 3 , X 4 is N; R2 is 0–4 substituents independently chosen from H, halogen, C 1-4 alkyl, CH 2 F, CHF 2 , CF 3 , OCF 3 , aryl, hetaryl, C 1-4 alkylOC 1-4 alkyl, C 1-4 alkylOaryl, C 1-4 alkylNR3R4, CO 2 R3, CONR3R4, CONR3SO 2 R4, nitro, NR3R4, C 1-4 alkylNR3R4, NR3COR4, NR5CONR3R4, NR3SO 2 R4, C 1-4 alkylNR3COR4, C 1-4 alkylNR5CONR3R4, C 1-4 alkylNR3SO 2 R4; and R3, R4 are each independently H, halogen, CH 2 F, CHF 2 , CF 3 , C 1-4 alkyl, C 1-4 alkyl cycloalkyl, C 1-4 cyclohetalkyl, aryl, C 1-4 alkyl aryl, hetaryl, C 1-4 alkyl hetaryl, or may be joined to form an optionally substituted 3–8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; and R5 is selected from H, C 1-4 alkyl, halogen, CH 2 F, CHF 2 , CF 3 , aryl or hetaryl; and R6 is selected from H, C 1-4 alkyl, aryl, hetaryl, C 1-4 alkyl aryl, C 1-4 alkyl hetaryl;

R1 is H, C 1-4 alkyl, C 1-6 cycloalkyl;

W is H, C 1-4 alkyl;

A is aryl, hetaryl optionally substituted with 0–3 substituents independently chosen from halogen, C 1-4 alkyl, CH 2 F, CHF 2 , CF 3 , OCF 3 , CN, nitro, NR8R9, aryl, hetaryl, C 1-4 aryl, C 14 hetaryl, C 1-4 alkylNR8R9, OC 1-4 alkylNR8R9, NR10C 1-4 NR8R9, NR8COR9, NR 10 CONR8R9, NR8SO 2 R9, CONR8R9, CO 2 R8 where R8 and R9 are each independently H, C 1-4 alkyl, aryl or which together form an optionally substituted 4–8 membered ring which may contain a heteroatom selected from O, S, NR11, where R11 is C 1-4 alkyl, and R10 is selected from H, C 1-4 alkyl.

3. A compound according to claim 1 where W is C 1-4 alkyl wherein the compound possesses S chirality at the chiral carbon bearing W.

4. A compound according to claim 3 wherein the compound is a mixture of R and S isomers and the mixture comprises at least 70% of the S isomer.

5. A compound according to claim 4 wherein the compound comprises at least 80% of the S isomer.

6. A compound according to claim 5 wherein the compound comprises at least 90% of the S isomer.

7. A compound according to claim 6 wherein the compound comprises at least 95% of the S isomer.

8. A compound according to claim 7 wherein the compound comprises at least 99% of the S isomer.

9. A compound according to claim 1 wherein the compound is selected from the group consisting of:

6-(1H-benzimidazol-1-yl)-N-[(1R)-1-phenylethyl]pyrazin-2-amine,

6-(1H-benzimidazol-1-yl)-N-[(1S)-1-(4-methoxyphenyl)ethyl]pyrazin-2-amine,

6-(1H-benzimidazol-1-yl)-N-[(1S)-1-(4-bromophenyl)ethyl]pyrazin-2-amine,

1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazole-6-carboxamide,

6-(1H-Benzimidazol-1-yl)-N-benzylpyrazin-2-amine,

1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazole-5-carboxamide,

6-(1H-Benzimidazol-1-yl)-N-(4-fluorobenzyl)pyrazin-2-amine,

6-{5-[(Morpholino-1-yl)carbonyl]-1H-benzimidazol-1-yl}-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

6-(1H-imidazo[4,5-b]pyridin-1-yl)-N-[(1R)-1-phenylethyl]pyrazin-2-amine,

6-{6-[(Morpholino-1-yl)carbonyl]-1H-benzimidazol-1-yl}-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

N-[1-(6-{[(1S)1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl

]cyclopropanecarboxamide, N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]nicotinamide,

N-[1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]cyclopropanecarboxamide,

6-(1H-Benzimidazol-1-yl)-N-[(1R)-1-phenylethyl]pyrazin-2-amine,

6-[6-(4,5-dihydro-1,3-oxazol-2-yl)-1H-benzimidazol-1-yl]-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

1-[6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl]-N-(2-hydroxyethyl)-1H-benzimidazole-6-carboxamide,

N-[1-(6-{[(1S) 1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]methanesulfonamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]methanesulfonamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]isonicotinamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]isonicotinamide,

6-(1H-Benzimidazol-1-yl)-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

6-[5-(4,5-dihydro-1,3-oxazol-2-yl)-1H-benzimidazo-1-yl]-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

1-[6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl]-N-(2-hydroxyethyl)-1H-benzimidazole-5-carboxamide,

6-(5-Methyl-1H-benzimidazol-1-yl)-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]nicotinamide,

N-methyl-1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazole-5-carboxamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]-2,2 -dimethylpropanamide,

N-methyl-1-(6-{[(1S)-1-phenylethyl]amino} pyrazin-2-yl)-1H-benzimidazole-6-carboxamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]-2,2 -dimethylpropanamide,

1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-amine,

2-Methoxy-N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]acetamide,

1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-amine,

2-Methoxy-N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]acetamide,

N-Benzyl-1-[6-([(1S)-1-phenylethyl]amino)pyrazin-2-yl]-1H-benzimidazole-5-carboxamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl] pyrazine-2-carboxamide,

1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-N-phenyl-1H-benzimidazole-5-carboxamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl] pyrazine-2-carboxamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]acetamide,

6-{5-[(4-Methylpiperazin-1-yl)methyl]-1H-benzimidazol-1-yl}-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

N-[1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]acetamide,

[1-(6-{[(1S)-1Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]methanol,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]benzamide,

[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]methanol,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]benzamide,

1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-N-[2-(dimethylamino)ethyl]-1H-benzimidazole-5-carboxamide,

1-[6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl]-N-(pyridin-3-ylmethyl)-1H-benzimidazol-5-amine,

tert-butyl (2S)-2-({[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]amino} carbonyl)pyrrolidine-1-carboxylate,

6-(3H-imidazo[4,5-c]pyridin-3-yl)-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

6-(1H-benzimidazol-1-yl)-N-[1-(4-fluorophenyl)ethyl]pyrazin-2-amine,

6-(1H-imidazo[4,5-c]pyridin-1-yl)-N-[(S)-1-phenylethyl]pyrazin-2-amine,

6-(1H-benzimidazol-1-yl)-N-[(1S)-1-(4-pyridin-3-ylphenyl)ethyl]pyrazin-2-amine,

(2S)-N-[1-(6-{[(1S)-1phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]pyrrolidine-2-carboxamide,

N-[(1S)-1-phenylethyl]-6-(5-pyridin-4-yl-1H-benzimidazol-1-yl)pyrazin-2-amine,

N-[(1S)-1-phenylethyl]-6-(5-pyridin-3-yl-1H-benzimidazol-1-yl)pyrazin-2-amine,

6-(5-bromo-1H-benzimidazol-1-yl)-N-[(1S)-1-phenylethyl]pyrazin-2-amine,

N-[3-(1H-imidazol-1-yl)propyl]-1-[6-([(1S)-1-phenylethyl]amino)pyrazin-2-yl]-1 H-benzimidazole-6-carboxamide,

N-1H-benzimidazole-6-carboxamide,

N-(3-morpholin-4-ylpropyl)-1-[6-([(1S)-1-phenylethyl]amino)pyrazin-2-yl]-1H-benzimidazole-6-carboxamide,

N-(3-morpholin-4-ylpropyl)-1-[6-([(1S)-1-phenylethyl]amino)pyrazin-2-yl]-1H-benzimidazole-5-carboxamide,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]piperidine-3-carboxamide,

6-(1H-benzimidazol-1-yl)-N-[(1S)-1-pyridin-3-ylethyl]pyrazin-2-amine,

6-(1H-benzimidazol-1-yl)-N-[(1S)-1-(1,1′-biphenyl-4-yl)ethyl]pyrazin-2-amine,

N-[1-(6-{[(1S)-1-phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]benzenesulfonamide, and

6-(1H-benzimidazol-1-yl)-N-[(1S)-1-(1,1′-biphenyl-4-yl)ethyl]pyrazin-2-amine.

10. A compound according to claim 1 wherein the compound is selected from the group consisting of:

11. A composition comprising a carrier and at least one compound according to claim 1 .